The overall objective of the BRC initiative is to provide technologies suitable to resolve the functional complexity of the living cell with emphasis on diffusive boundary layers surrounding cells and tissues and correlating the data to the activity of the cell in sub-cellular domains. That initiative requires a continuous development of electrochemical micro-sensors and their applications for detection of important biological molecules through collaborative research projects. This proposal is a continuation of previous research efforts in scope of sensor speed, selectivity and "poisoning" by compounds used in experimental conditions. Major improvement of the sensor performance is claimed in sensor construction. The applicants plan to pursue the sensor construction with a commercial initiative -BioCurrents Research Inc. (BRI) - assuming successful funding of Phase II STTR award or to continue independently. Furthermore, it is planned to continue the development of the BioKelvin probe now renamed to the Bioelectric Field Imager (BFI) device with a goal of clinical application to skin disease within a collaborative work with General Medicine. There are 4 specific aims within the 4A: 1; (1) to continue investigation of ISE in "self-referencing mode" (Seris), (2) to continue development of amperometric -redox based electrodes in self-referencing mode (Sera) (a) by continuing further development of existing electrodes and (b) by initiating development of application of new sensors design -sol-gels and Os gels, (3) to continue development and innovation in hardware and software support, and (4) to improve production of the Whalen design amperometric O2 sensor.